When it comes to breast cancer, anti-HER2 therapy has to be mentioned. HER2-targeted drugs, represented by trastuzumab, have become the foundation of breast cancer treatment.
Since HER2 is so important, what exactly is it?What does it mean to be HER2 positive?HER2 is a growth factor receptor on cells, the full Chinese name is human epidermal growth factor receptor 2. HER2 receives stimulatory messages that accelerate cancer cell growth and division.
HER2 positive breast cancers account for about 20% of all breast cancers, and HER2 positive predicts a high degree of tumor malignancy and a relatively poor prognosis for patients. In addition, HER2 positive breast cancer is a complex disease that may vary in pathogenesis and respond differently to drugs in different patients, ultimately presenting differential disease characteristics and treatment outcomes.
Trastuzumab significantly reduces the risk of death from HER2 positive breast cancer and gives patients better survival, yet some people still respond poorly to trastuzumab treatment.
After trastuzumab, only a few “upgraded” anti HER2 targeted drugs are available. The new targeted drugs are used in combination with trastuzumab in an attempt to “kill the chain” to eliminate breast cancer. Pertuzumab is an “upgraded” anti-HER2-targeted therapy.
How pertuzumab works against cancer
Pattuzumab is a monoclonal antibody that binds to HER2 in a different location than trastuzumab. Patuximab inhibits HER2 from heterodimerizing with other members of the HER family and is therefore more resistant to HER2.
HER2 positive advanced breast cancer, dual-targeted therapy with patuximab + trastuzumab to improve outcomes
Can the powerful combination of patuximab and trastuzumab further improve survival in patients with HER2-positive advanced breast cancer?
A clinical study called CLEOPATRA answered this question. This study involved more than 800 breast cancer patients, half of whom received the triple combination of pertuzumab + trastuzumab + docetaxel.
The New England Journal of Medicine, the world’s leading medical journal, reported results at a follow-up of 50 months:
- The addition of pertuzumab resulted in a significant increase in disease remission in patients, from 69% to 80% .
- Pattuzumab combined with trastuzumab and chemotherapy increased the median survival time by 15.7 months to 56.5 months and reduced the risk of death by 32%.
- Progression-free survival was prolonged by 6.3 months (to 12.4 months and 18.7 months, respectively) and the risk of progressive breast cancer progression was reduced by 32% with pertuzumab treatment.
As we can see from the data above, the “double whammy” of pertuzumab combined with trastuzumab can lead to better survival in patients with HER2-positive advanced breast cancer. on June 8, 2012, pertuzumab was approved in the United States for HER2 positive metastatic breast cancer.
What is the safety profile of patuximab?
Even with targeted therapies, there is some degree of side effects. The three-drug regimen of patuximab + trastuzumab + docetaxel inevitably increases the number of adverse effects while improving efficacy. Common ones include diarrhea (67%), neutropenia (53%), rash (34%), mucosal inflammation (27%), dry skin (10%), and severe febrile neutropenia (14%).
Overall, dual-targeted therapy with patuximab in combination with trastuzumab did not significantly increase cardiotoxicity in patients, but the incidence of other side effects, such as diarrhea, was slightly higher.
Pattuzumab alone is generally effective
Does the dual-targeted anti-HER2 therapy help patients get better survival, and is this due to patuximab itself or the combined effect of patuximab + trastuzumab?
One study initially explored this question by selecting 29 patients with advanced breast cancer who had failed first-line trastuzumab and were treated with patuximab alone. If pertuzumab was also resistant, the combination of pertuzumab + trastuzumab was continued.
This pattern of dosing strings together trastuzumab and pertuzumab. The 29 patients treated with only patuximab in the first phase had a disease remission rate of only about 10%. With subsequent dual-targeted therapy, patients had clinical remission rates of more than 40%, and patients had significantly longer progression-free survival (17.4 weeks versus 7.1 weeks).
Pattuzumab in China
In 2018 January 2018, a marketing application for patuximab was submitted in China, but it has not yet been approved.
Currently, there are several clinical studies of pertuzumab for breast cancer underway in China (No. CTR20160366, CTR20131049, CTR20130952, CTR20150679, CTR20131487, etc.). We look forward to landing patuximab soon to provide more treatment options for breast cancer patients.
Summary
- The advent of patuximab is another advance in anti HER2 therapy for breast cancer. A dual-targeted regimen of trastuzumab plus pertuzumab, with appropriate addition of chemotherapy drugs, is available for first-line treatment of patients with advanced disease. Studies have confirmed that this three-drug regimen can increase patient survival by more than 1 year.
- Two-targeted therapy with patuximab + trastuzumab did not significantly increase cardiotoxicity in patients, but other side effects such as increased diarrhea and a slight increase in hematologic toxicity were noted.
- Targeted drugs are expensive, and dual-targeted therapy is more expensive and may reduce drug accessibility.
Treatment of breast cancer has gotten better over the past decade or so, and anti-HER2 targeted therapies have been responsible for this. The imminent arrival of patuximab holds the promise of renewing the saga of trastuzumab in breast cancer.